Anti-microbial coating physical vapor deposition such as cathodic arc evaporation

ABSTRACT

A bioactive coated substrate includes a base substrate, a first interlayer disposed over the base substrate, an outermost bioactive layer disposed on the first interlayer, and a topcoat layer disposed on the outermost bioactive layer. Characteristically, a plurality of microscopic openings extending through the topcoat layer and the outermost bioactive layer expose the first interlayer and the outermost bioactive layer. A method for forming the bioactive coated substrate is also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.17/342,887 filed Jun. 9, 2021, which, in turn, claims the benefit ofU.S. provisional application Ser. No. 63/039,015 filed Jun. 15, 2020,the disclosures of which are hereby incorporated in their entirety byreference herein.

TECHNICAL FIELD

In at least one aspect, the present invention relates to a coatingsystem with bioactive properties that is formed by physical vapordeposition and related methods.

BACKGROUND

Physical vapor deposition (PVD) is a technique for thin film formationor coating a substrate. PVD involves vaporization of a material thatthen condenses on a surface, forming a coating layer. PVD can result inthe deposit of macroparticles, which are often considered a defect. Themacroparticles may be loosely bound to the coated layer. Mechanicalprocesses can be used to remove these macroparticles, but removal leavespinholes, which are also often considered defects. For example, cathodicarc evaporation (CAE), a form of PVD, involving a high current, lowvoltage arc on the surface of a cathodic target produces macroparticles.Because macroparticles and pinholes are recognized as defects, greateffort to eliminate or reduce the size and quantity of macroparticles isafforded.

Coatings with bioactive properties can be useful for various purposes.Bioactive refers to a material having biological effects orphysiological effects on living things. For example, a bioactivematerial includes a material resulting in a modification in the normalbiological function or a physiological mechanism of a living thing.Bioactive, as used herein, includes beneficial and detrimental effectsto microorganisms or modifications to the normal functioning of amicroorganism. One common bioactive material is antimicrobialsubstances. Antimicrobial coatings serve many purposes. Generally,antimicrobial coatings inhibit the growth or kill microbes like viral,bacterial or fungal organisms. One particularly relevant exampleincludes preventing the spread of communicable diseases by the use ofantimicrobial materials. Antimicrobial materials may also serve hygienicpurposes. The desire to prevent the spread of disease and for heightenedhygiene has resulted in significant efforts to develop antimicrobialmaterials. The use of antimicrobial materials in health care facilitiesand health treatments can provide significant benefits. Healthfacilities, such as hospitals, present unique environments that combinehigh concentrations of germs and individuals with vulnerable immunities.Therefore, facilities such as hospitals greatly benefit fromantimicrobial surfaces. Antimicrobial materials for medical equipmentcan reduce the burden of disinfecting and prevent the spread of disease.Further, affordable antimicrobial surfaces could present benefits on anysurface that comes into contact with living things. For example,surfaces involved in cooking or commonly touched surfaces like doorknobscould greatly benefit from antimicrobial properties. Even primarilydecorative surfaces, if affordable, could benefit from antimicrobialcharacteristics and assist in inhibiting the spread and growth ofharmful or undesirable antimicrobial life.

But producing antimicrobial materials can be difficult and expensive.Further, antimicrobial properties may have other undesirable properties.For example, some antimicrobial materials may be too soft. Otherantimicrobial materials may have poor abrasion resistance. Microban® isan antimicrobial coating that includes silver particles dispersed in anorganic matrix. Antimicrobial coatings involving an organic matrix mayhave the aesthetic appearance of paint. In some applications, theappearance of paint may be undesirable. Some antimicrobial coatings mayuse nanoparticle vapor deposition to deposit nanoparticles withantimicrobial properties on the surface of a coating. For example,ABACO® from Protec, is an antimicrobial coating using nanoparticles.However, the use of nanoparticles can be complex and expensive. Furthersuch coatings may have delicate surfaces or poor abrasion resistance.Another example of antimicrobial materials includes various metals. Forexample, silver is known to have antimicrobial properties. However, asstated above silver can be expensive, and its properties may not besuitable for many applications. For example, the appearance or abrasionresistance of silver may be unsuitable for certain applications.

Accordingly, there is a need for an antimicrobial coating that solvesone or more of these problems or offers an alternative to currentantimicrobial materials.

SUMMARY

In at least one aspect, a bioactive coated substrate is provided. Thebioactive coated substrate includes a base substrate, a first bioactivelayer disposed over the base substrate, and a topcoat layer disposed onthe outermost bioactive layer. Characteristically, the topcoat layerdefines a plurality of microscopic openings that expose the outermostbioactive layer.

In another aspect, a bioactive coated substrate is provided. Thebioactive coated substrate includes two or more layers (e.g.,alternating) of bioactive material and an inert material where the inertlayer always on top. The bioactive coated substrate includes pits orcracks with exposure of some combination of rings and spots of bioactivematerial. Bioactive materials are compounds and alloys of Cu (e.g., Cu,Cu₂O, CuO, brass, bronze) while inert materials include compounds andalloys of Zr, Ti, Cr, DLC. The bioactive coated substrate can include ahydrophobic layer includes a SiOx adhesion layer and a fluorinatedpolymer layer.

In another aspect, a method of forming the bioactive coated substrateset forth herein is provided. The method includes steps of providing abase substrate and then depositing an outermost bioactive layer over thesubstrate. The outermost bioactive layer has a plurality ofmacroparticles extending from a surface of the outermost bioactivelayer. Otherwise, macroparticles extending from the surface are appliedto the outermost bioactive layer. A topcoat layer is deposited on theoutermost bioactive layer. Characteristically, the pluralitymacroparticles extend into the topcoat layer. At least a portion of theplurality macroparticles is removed to form a plurality of microscopicopenings in the topcoat layer down to the outermost bioactive layer.

In another aspect, a bioactive coated substrate is provided. Thebioactive coated substrate includes a base substrate, a first interlayerdisposed over the base substrate, an outermost bioactive layer disposedon the first interlayer, and a topcoat layer disposed on the outermostbioactive layer. A plurality of microscopic openings extending throughthe topcoat layer and the outermost bioactive layer expose the firstinterlayer and the outermost bioactive layer. Characteristically, theplurality of microscopic openings originating in the first interlayer.

In still another aspect, a method for forming a bioactive coatedsubstrate is provided. The method includes steps of providing a basesubstrate and depositing a first interlayer over the base substrate. Thefirst interlayer includes a plurality of macroparticles protruding fromthe surface of the first interlayer. An outermost bioactive layer isdeposited over the first interlayer where the plurality ofmacroparticles extends into the outermost bioactive layer. A topcoatlayer is deposited on the outermost bioactive layer where the pluralityof macroparticles extends into the topcoat layer. Finally, at least aportion of the plurality of macroparticles is removed to form aplurality of microscopic openings in the topcoat layer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a cross-sectional view of a variation of a bioactive coatedsubstrate having a plurality of microscopic openings.

FIG. 1B is a cross-sectional view of a variation of a bioactive coatedsubstrate having a plurality of microscopic openings.

FIG. 1C is a cross-sectional view of a variation of a bioactive coatedsubstrate having a plurality of microscopic openings.

FIG. 1D is a top view of a variation of a bioactive coated substratehaving a plurality of microscopic openings.

FIG. 2A is a cross-sectional view of a variation of a bioactive coatedsubstrate having multiple bioactive layers a plurality of microscopicopenings in the topcoat layer.

FIG. 2B is a cross-sectional view of a variation of a bioactive coatedsubstrate having multiple bioactive layers a plurality of microscopicopenings in the topcoat layer.

FIG. 2C is a cross-sectional view of a variation of a bioactive coatedsubstrate having multiple bioactive layers a plurality of microscopicopenings in the topcoat layer.

FIG. 3A is a cross-sectional view of a precursor-coated substrate havinga single bioactive layer with a plurality of macroparticles and atopcoat layer.

FIG. 3B is a cross-sectional view of a precursor coated substrate havingmultiple bioactive layers with an outermost bioactive layer having aplurality of macroparticles.

FIG. 4 is a cross-sectional view of a bioactive coated substrate coatedwith a hydrophobic layer.

FIG. 5 is a flow chart depicting a method for preparing a bioactivecoated substrate.

FIG. 6 provides Table 1 which shows the properties of bioactive coatedsubstrates and a copper penny.

FIG. 7 provides Table 2 which shows results for the growth of bacteria(i.e., S. aureus) on stainless steel, brass, a multilayer sample havinga buried active layer with microscopic openings, and a sample with thebioactive layer on top.

FIG. 8 provides top surface elemental mapping (EDS) of a bioactivecoated substrate.

FIG. 9 provides SEM cross-section images of a bioactive coatedsubstrate.

DETAILED DESCRIPTION

Reference will now be made in detail to presently preferredcompositions, embodiments and methods of the present invention, whichconstitute the best modes of practicing the invention presently known tothe inventors. The Figures are not necessarily to scale. However, it isto be understood that the disclosed embodiments are merely exemplary ofthe invention that may be embodied in various and alternative forms.Therefore, specific details disclosed herein are not to be interpretedas limiting, but merely as a representative basis for any aspect of theinvention and/or as a representative basis for teaching one skilled inthe art to variously employ the present invention.

Except in the examples, or where otherwise expressly indicated, allnumerical quantities in this description indicating amounts of materialor conditions of reaction and/or use are to be understood as modified bythe word “about” in describing the broadest scope of the invention.Practice within the numerical limits stated is generally preferred.Also, unless expressly stated to the contrary: percent, “parts of,” andratio values are by weight; the description of a group or class ofmaterials as suitable or preferred for a given purpose in connectionwith the invention implies that mixtures of any two or more of themembers of the group or class are equally suitable or preferred;description of constituents in chemical terms refers to the constituentsat the time of addition to any combination specified in the description,and does not necessarily preclude chemical interactions among theconstituents of a mixture once mixed; the first definition of an acronymor other abbreviation applies to all subsequent uses herein of the sameabbreviation and applies mutatis mutandis to normal grammaticalvariations of the initially defined abbreviation; and, unless expresslystated to the contrary, measurement of a property is determined by thesame technique as previously or later referenced for the same property.

It must also be noted that, as used in the specification and theappended claims, the singular form “a,” “an,” and “the” comprise pluralreferents unless the context clearly indicates otherwise. For example,reference to a component in the singular is intended to comprise aplurality of components.

The phrase “composed of” means “including” or “comprising.” Typically,this phrase is used to denote that an object is formed from a material.

The term “comprising” is synonymous with “including,” “having,”“containing,” or “characterized by.” These terms are inclusive andopen-ended and do not exclude additional, unrecited elements or methodsteps.

The phrase “consisting of” excludes any element, step, or ingredient notspecified in the claim. When this phrase appears in a clause of the bodyof a claim, rather than immediately following the preamble, it limitsonly the element set forth in that clause; other elements are notexcluded from the claim as a whole.

The phrase “consisting essentially of” limits the scope of a claim tothe specified materials or steps, plus those that do not materiallyaffect the basic and novel characteristic(s) of the claimed subjectmatter.

With respect to the terms “comprising,” “consisting of,” and “consistingessentially of,” where one of these three terms is used herein, thepresently disclosed and claimed subject matter can include the use ofeither of the other two terms.

The term “substantially,” “generally,” or “about” may be used herein todescribe disclosed or claimed embodiments. The term “substantially” maymodify a value or relative characteristic disclosed or claimed in thepresent disclosure. In such instances, “substantially” may signify thatthe value or relative characteristic it modifies is within ±0%, 0.1%,0.5%, 1%, 2%, 3%, 4%, 5% or 10% of the value or relative characteristic.

It should also be appreciated that integer ranges explicitly include allintervening integers. For example, the integer range 1-10 explicitlyincludes 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. Similarly, the range 1 to100 includes 1, 2, 3, 4 . . . . 97, 98, 99, 100. Similarly, when anyrange is called for, intervening numbers that are increments of thedifference between the upper limit and the lower limit divided by 10 canbe taken as alternative upper or lower limits. For example, if the rangeis 1.1. to 2.1 the following numbers 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8,1.9, and 2.0 can be selected as lower or upper limits. In the specificexamples set forth herein, concentrations, temperature, and reactionconditions (e.g. pressure, flow rates, etc.) can be practiced with plusor minus 50 percent of the values indicated rounded to three significantfigures. In a refinement, concentrations, temperature, and reactionconditions (e.g., pressure, flow rates, etc.) can be practiced with plusor minus 30 percent of the values indicated rounded to three significantfigures of the value provided in the examples. In another refinement,concentrations, temperature, and reaction conditions (e.g., flow rates,etc.) can be practiced with plus or minus 10 percent of the valuesindicated rounded to three significant figures of the value provided inthe examples.

In the examples set forth herein, concentrations, temperature, andreaction conditions (e.g., pressure, flow rates, etc.) can be practicedwith plus or minus 50 percent of the values indicated rounded to ortruncated to two significant figures of the value provided in theexamples. In a refinement, concentrations, temperature, and reactionconditions (e.g., pressure, flow rates, etc.) can be practiced with plusor minus 30 percent of the values indicated rounded to or truncated totwo significant figures of the value provided in the examples. Inanother refinement, concentrations, temperature, and reaction conditions(e.g., pressure, flow rates, etc.) can be practiced with plus or minus10 percent of the values indicated rounded to or truncated to twosignificant figures of the value provided in the examples.

For all compounds expressed as an empirical chemical formula with aplurality of letters and numeric subscripts (e.g., CH₂O), values of thesubscripts can be plus or minus 50 percent of the values indicatedrounded to or truncated to two significant figures. For example, if CH₂Ois indicated, a compound of formulaC_((0.8-1.2))H_((1.6-2.4))O_((0.8-1.2)). In a refinement, values of thesubscripts can be plus or minus 30 percent of the values indicatedrounded to or truncated to two significant figures. In still anotherrefinement, values of the subscripts can be plus or minus 20 percent ofthe values indicated rounded to or truncated to two significant figures.

The thickness of all layers described herein can have a thickness from50 to 1500 nm unless explicitly stated to the contrary.

Abbreviations

“CAE” means cathodic arc evaporation.

“EDS” means Energy-dispersive X-ray spectroscopy.

“PVD” means physical vapor deposition.

“SEM” means scanning electron microscopy.

“XRF” means X-ray fluorescence.

The term “microscopic opening” refers to an opening that has at leastone spatial dimension that is less than 15 microns.

Referring to FIGS. 1A, 1B, and 1C, a schematic cross-section of asubstrate coated with a bioactive material is provided. Bioactive coatedsubstrate 10 includes a base substrate 12 and a first interlayer 14disposed over and optionally contacting the substrate. In a refinement,first interlayer 14 has a thickness from about 50 to 1500 nm. The term“base substrate” refers to the substrate before is coated to form thebioactive substrate set forth below. Outermost bioactive layer 16 isdisposed over and optionally contacts first interlayer 14. As used, theterm “outermost bioactive layer” refers to the bioactive layer furthestfrom the base substrate. In a refinement, outermost bioactive layer 16has a thickness from about 50 to 5000 nm. In a refinement, bioactivecoated substrate 10 also includes a topcoat layer 18 disposed over andoptionally contacting the topcoat layer. In a refinement, topcoat layer18 has a thickness from about 50 to 1500 nm.

Characteristically, a plurality of microscopic openings 20 exposesoutermost bioactive layer 16 to ambient. In a refinement, the pluralityof holes includes an opening type selected from the group of pores,pinholes, pits, and combinations thereof. In this regard, FIG. 1Dprovides a top view from the topcoat layer side illustrating theexposure of the underlying layers. The plurality of openings 20 is atleast partially defined by topcoat layer 18. The plurality ofmicroscopic openings 20 can be further defined by outermost bioactivelayer 16 and first interlayer 14 depending on how deep the microscopicopenings extend. Typically, the microscopic openings have an averagewidth w₁ of about 100 nm to 10 microns. In this context, “width” means adistance between walls extending from the microscopic opening bottom 21that defines each opening. In a further refinement, the topcoat layer 18defines at least about 1 microscopic opening per square millimeter.Alternatively, the width w₁ is the minimum diameter of a circularcylinder that can enclose a microscopic opening. In some refinements,the topcoat layer 18 defines in increasing order of preferences, atleast about 1 microscopic opening per square millimeter, at least about2 microscopic openings per square millimeter, at least about 3microscopic openings per square millimeter, at least about 4 microscopicopenings per square millimeter, or at least about 5 microscopic openingsper square millimeter.

In a refinement, base layer 22 is interposed between substrate 12 andfirst interlayer 14. Base layer 22 optionally contacts substrate 12 andan interlayer (e.g., first interlayer 14) on opposite faces. In arefinement, the base layer is composed of a component selected from thegroup consisting of zirconium carbonitride, zirconium nitride, zirconiumoxycarbide, zirconium oxynitride, and zirconium oxycarbonitride. Baselayer 22 when present typically has a thickness from about 20 to 300 nm.It should be appreciated that the present embodiment is not limited bythe particular deposition methods for depositing outermost bioactivelayer 16 and topcoat layer 18. For example, these layers can be made byCVD, PVD which could be sputtering, or CAE.

Outermost bioactive layer 16 and topcoat layer 18 can be applied to anysuitable substrate 12. A suitable substrate 12 can be composed of anymaterial that exhibits thermal stability at an operational (i.e., thetemperature that the bioactive coated substrate is used at) ordeposition temperatures for each of the layers. In particular, substrate12 should be thermally stable at a temperature of at least 80° C. In arefinement, the substrate 12 should be thermally stable at a temperatureof at least 250° C. In some refinements, a suitable substrate 12 can becomposed of any material that is electrically conductive. For example,suitable materials that the base substrate can be composed of include,but are not limited to, metals, metal alloys, and/or carbon materials.Additional examples of suitable materials that the base substrate can becomposed of include, but are not limited to, stainless steel,chromium-nickel plated brass, chromium-nickel-copper plated zinc,chromium-nickel-copper plated ABS plastic and chromium-nickel-copperplated aluminum.

In some variations as depicted in FIGS. 1A, 1B, and 1C, the microscopicopenings narrow along a direction perpendicular to the base substrate12.

In the variation depicted in FIG. 1A, the topcoat layer defines aplurality of microscopic openings that expose the first interlayer 14and the outermost bioactive layer 16. In this regard, at least a subsetof the microscopic openings extend to first interlayer 14.

In the variation depicted in FIG. 1B, the topcoat layer defines aplurality of microscopic openings that only expose the outermostbioactive layer 16. In this regard, at least a subset of the microscopicopenings extends to the outermost bioactive layer 16. In thisrefinement, first interlayer 14 is optional.

In the variation depicted in FIG. 1C, the topcoat layer definesmicroscopic openings that expose the first interlayer 14 and theoutermost bioactive layer 16. In this regard, a first subset of themicroscopic openings extend to the first interlayer 14 and a secondsubset of the microscopic openings extend only to the outermostbioactive layer 16.

FIGS. 2A, 2B, and 2C provide schematic cross-sections of a bioactivecoated substrate 10′ having a multilayer stack 24 that includes one ormore additional bioactive layers 16′ alternating with one or moreadditional interlayers 14′. The multilayer stack 24 is interposedbetween the base substrate 12 and the first interlayer 14.Characteristically, additional microscopic openings extend to amicroscopic opening bottom 28 such that any layer above microscopicopening bottom 28 is exposed to ambient. In particular, that firstbioactive layer 16, any additional bioactive layer 16′, first interlayer14, and any additional interlayers 14′ above the microscopic openingbottom, the microscopic opening bottom interlayer, and each interlayerabove the microscopic opening bottom interlayer are exposed to ambient.A set forth above, topcoat layer 18 is disposed over outermost bioactivelayer 16. In one refinement, the additional microscopic openingsoriginate from an interlayer. In another refinement, the additionalmicroscopic openings originate from a bioactive layer. In still anotherrefinement, additional microscopic openings originate from brothinterlayers and bioactive layers. Typically, there can be 1 to 10additional bioactive layers 16′ and 1 to 10 interlayers 14′. It shouldbe appreciated that microscopic openings 20 can extend to outermostbioactive layer 16 and/or to any of the additional interlayers 14′and/or to any of the additional bioactive layers 16′. In a refinement,the first interlayer 14 and additional interlayers 14′ can be composedof zirconium carbonitride, zirconium nitride, zirconium oxycarbide,zirconium oxynitride, or zirconium oxycarbonitride. In anotherrefinement, the additional interlayers 14′ can also be bioactive layersbut with a different thickness and/or stoichiometry than the bioactivelayers, it contacts on opposite faces. In this regard, interlayers 14can be composed of various copper alloys, as set forth below. In anotherrefinement, the first interlayer 14 and additional interlayers 14′ canbe composed of a metal nitride. For example, the first interlayer 14 andadditional interlayers 14′ can be composed of zirconium nitride (ZrN),titanium nitride (TiN), zirconium oxycarbides (ZrOC), zirconium oxides(ZrO₂), diamond-like-carbon (DLC) or a combination thereof.

In some variations as depicted in FIGS. 2A, 2B, and 2C, the microscopicopenings narrow along a direction perpendicular to the base substrate12.

In the variation depicted in FIG. 2A, the topcoat layer defines aplurality of microscopic openings that expose the first interlayer 14,additional interlayers 14′, the outermost bioactive layer 16, andadditional bioactive layers 14′. In this regard, at least a subset of orall of the microscopic openings extend to first interlayer 14 and/or theadditional interlayers 14′.

In the variation depicted in FIG. 2B, the topcoat layer defines aplurality of microscopic openings that expose the first interlayer 14,additional interlayers 14′, the outermost bioactive layer 16, andadditional bioactive layers 14′. In this regard, at least a subset of orall the microscopic openings extends to the outermost bioactive layer 16and additional bioactive layers 16′.

In the variation depicted in FIG. 2C, the topcoat layer defines aplurality of microscopic openings that expose the first interlayer 14,additional interlayers 14′, the outermost bioactive layer 16, andadditional bioactive layers 14′. In this regard, a first subset of themicroscopic openings extend to first interlayer 14 and additionalinterlayers 14′ and a second subset of the microscopic openings extendto the outermost bioactive layer 16 and additional bioactive layers 16′.

In a variation, the plurality of microscopic openings 20 is formed froma plurality of macroparticles formed on a surface of or within one ormore of first interlayer 14, outermost bioactive layer 16, additionalinterlayer 14′, additional bioactive layers 16′ the outermost bioactivelayer 16 during deposition of that layer as set forth below. In thiscontext, the term “macroparticles” refers to particles having at leastone spatial dimension greater than 100 nm. Typically, cathodic arcdeposition and CAE can form such macroparticles while sputtering tendsto form smooth layers without such particles. The macroparticles extendinto the topcoat layer and are subsequently removed as described belowin more detail to form the microscopic openings.

Other techniques can be used to expose the bioactive layers andinterlayers. For example, masking and selective etching as inphotolithography can be used to expose the bioactive layers andinterlayers. In another refinement, the top layer can be porous throughcolumnar growth or, like with electroplating. In still anotherrefinement, bioactive layers and interlayers can be exposed throughmicrocracking or pitting by applying a stressed layer. In yet anotherrefinement, the top layer could be partially removed by mechanical meanslike scratching or drilling. In another, bioactive layers andinterlayers can be deposited with crack or pits or porosity.

In another variation, base layer 22, the first interlayer 14, andadditional interlayers 14′ are independently composed of zirconium ortitanium, carbon, and nitrogen where zirconium is present in an amountof at least 50 mole percent with each of the carbon and nitrogen presentin an amount of at least 0.02 and 0.1 mole percent, respectively. In arefinement, base layer 22 and interlayers 14 are independently composedof a compound having the following formula:

M_(1-x-y)C_(x)N_(y)

where M is zirconium or titanium and x is 0.0 to 0.3 and Y is 0.1 to0.5. In a refinement, x is 0.0 to 0.2 and y is 0.2 to 0.3. In anotherrefinement, x is at least in increasing order of preference 0.0, 0.02,0.03, 0.04, 0.05, 0.07, or 0.09 and at most in increasing order ofpreference, 0.5, 0.4, 0.3, 0.25, 0.2, 0.15, or 0.11. Similarly, in thisrefinement, y is at least in increasing order of preference 0.1, 0.15,0.2, 0.25, 0.27, or 0.29 and at most in increasing order of preference,0.6, 0.5, 0.40, 0.35, 0.33, or 0.31. In a further refinement, the baselayer is composed of zirconium carbonitride described byZr_(0.60)C_(0.10)N_(0.30).

In still another variation, base layer 22, the first interlayer 14, andadditional interlayers 14′ are independently composed of zirconium ortitanium, carbon, and oxygen where zirconium is present in an amount ofat least 50 mole percent with each of the carbon and oxygen present inan amount of at least 0.02 and 0.1 mole percent, respectively. In arefinement, base layer 22 and interlayers 14 independently areindependently composed of a compound having the following formula:

M_(1-x-y)O_(x)C_(y).

where M is zirconium or titanium and x is 0.1 to 0.4 and y is 0.5 to0.2. In a further refinement, the base layer is composed of zirconiumoxycarbide described by Zr_(0.50)O_(0.35)C_(0.15).

Bioactive layer 16 and any additional bioactive layers 16′ can be anymaterial with bioactive properties. In particular, the bioactive layer16 and any additional bioactive layers 16′ are antimicrobial layers.Therefore, bioactive layer 16 and any additional bioactive layers 16′can include a material with antimicrobial properties. In a refinement,the bioactive layer 16 and any additional bioactive layers 16′ can becomposed of a metal or metal-containing compound with antimicrobialproperties. For example, bioactive layer 16 and any additional bioactivelayers 16′ can be composed of a metal, a metal oxide, a metal alloy orany combination thereof. In another refinement, bioactive layer 16 andany additional bioactive layers 16′ can be composed of a componentselected from the group consisting of include copper alloys, orcopper-containing compounds. Such copper-containing compounds includecopper atoms in the +1 or +2 oxidation state or combinations of copperatoms thereof. Examples of copper-containing compounds include, but arelimited to copper, copper oxides, copper nitrides, copper oxidescontaining carbon atoms, and combinations thereof. In one variation,copper alloys include copper and nickel. Typically, each copper alloyincludes nickel in an amount from about 8 to 28 weight percent of thetotal weight of the bioactive layer with the copper being present in anamount from about 72 to 92 weight percent of the total weight of thebioactive layer. In a refinement, the copper alloy includes nickel in anamount from about 10 to 25 weight percent of the total weight of thebioactive layer and copper in an amount form about 75 to 90 weightpercent of the total weight of the bioactive layer. In some variations,the copper alloy can independently include additional elements such asiron, zirconium, tungsten, chromium, and combinations thereof. In arefinement, each of these additional elements is independently presentin an amount from about 0.01 to about 5 weight percent of the totalweight of the bioactive layer. In a refinement, each of these additionalelements are independently present in an amount from about 0.01 to about5 weight percent of the total weight of the bioactive layer. Examples ofcopper alloys are CuVerro® White Bronze and CuVerro® Rose commerciallyavailable from Olin Brass located in Louisville, Ky.

In other variations, the bioactive layer 16 and any additional bioactivelayers 16′ include silver, a silver alloy, a silver-containing compound(e.g., a silver oxide), or any combination thereof. Other metals thatcan exhibit antimicrobial properties include but are not limited togallium (Ga), gold (Au), magnesium (Mg), titanium (Ti), and zinc (Zn).The bioactive layers 16 and 16′ can include a combination of metals,metal oxides or metal alloys. This includes, for example, a bioactivelayer 16 that includes copper (Cu) and silver (Ag).

In one refinement, each of the one or more of the bioactive layer 16 andany additional bioactive layers 16′ are independently composed ofCuO_(x), where x is from 0.1 to 1.0. In another refinement, each of theone or more of the bioactive layers 16 and 16′ independently composed ofCuO_(a)N_(b), where a is from 0.0 to 1.2 and b, is from 0.01 to 0.4. Instill another refinement, each of the one or more of the bioactive layer16 and any additional bioactive layers 16′ independently composed ofCuO_(c)C_(d), where c is from 0.0 to 1.2 and d, is from 0.01 to 0.4. Ina variation, each of the one or more of the bioactive layers 16 and 16′independently composed of any combination of copper metal, CuO_(x),CuO_(a)N_(b), and CuO_(c)C_(d); Therefore, each of the one or more ofthe bioactive layers 16 and 16′ independently composed of a combinationof copper metal, CuO_(x), CuO_(a)N_(b), and CuO_(c)C_(d) or acombination of copper metal and CuO_(x) or a combination of copper metaland CuO_(a)N_(b), a mixture of copper metal and CuO_(c)C_(d) or acombination of copper metal, CuO_(x), and CuO_(a)N_(b) or a combinationof copper metal, CuO_(x) and CuO_(c)C_(d) or a combination of coppermetal, CuO_(a)N_(b), and CuO_(c)C_(d) or a combination of CuO_(x),CuO_(a)N_(b), and CuO_(c)C_(d) or a combination of CuO_(x) andCuO_(a)N_(b) or a combination of CuO_(a)N_(b), and CuO_(c)C_(d) or acombination of CuO_(x), CuO_(a)N_(b), and CuO_(c)C_(d). Some suitablebioactive layers can be composed of Cu_(x)O_(y), Cu_(x)N_(y),Cu_(x)O_(y)N_(z), and Cu_(x)O_(y)C_(z) where x can be 1, 2, or 3; y canbe 1, 2, or 3; and z can be 1, 2, or 3.

Advantageously, topcoat layer 18 provides a number of useful propertiesto the bioactive coated substrate. For example, the topcoat layer 18 canprovide improved abrasion resistance. In particular, the topcoat layer18 can provide a higher abrasion resistance than outermost bioactivelayer 16. A topcoat layer 18 with higher abrasion resistance can reducewear to the surface of outermost bioactive layer 16. In anotherrefinement, bioactive coated substrate 10 includes an antimicrobiallayer and a topcoat layer 18 with a higher abrasion resistance can besuitable for a surgical tool or instrument. In addition to abrasionresistance, other useful properties of the topcoat layer 18 includedetermining the final color/appearance of the coating and corrosionresistance. The abrasion resistance can be determined by ISO 28080. Thetopcoat layer 18 is not limited to providing abrasion resistance. Forexample, the topcoat layer 18 can provide improved hardness, impactresistance and/or toughness. In another example, the topcoat layer 18can provide an appealing or desired aesthetic effect. For example, thetopcoat layer can be chromium. Topcoat layer 18 can also impart improvedhardness to the bioactive coated substrate. The topcoat layer 18 can beapplied by any suitable deposition technique such as PVD and CAE. In arefinement, topcoat layer 106 can be composed of carbides, gold,graphite, nitrides, platinum, titanium, or titanium nitride, Zr, ZrN,ZrCN, ZrON, ZrO₂, ZrOC, Cr, CrN, CrCN, Ti, TiN, TiCN, TiON, TiO₂, andTiOC.

In a variation, the layer immediately below the outermost bioactivelayer 16 can be used as an indicator layer that the outermost bioactivelayer 16 has worn away. Such an indicator layer can serve as a visualindication that the outermost bioactive layer 16 is compromised. Forexample, the indicator can have a distinctly different color from thebioactive layer 16 and thus serve to visually alert a user that theoutermost bioactive layer 16 is compromised. With respect to setting thecolor of the various layers so that color differences can be determined,it should be appreciated that the color of each of the layers set forthabove can independently be changed by adjusting the thicknesses and orstoichiometries of the layer. In a refinement, the indicator layer canbe another metal, alloy or metal-containing compound with a distinctlydifferent color. Advantageously, the bioactive coated substrate is suchthat the color of the top most (from the substrate) bioactiveantimicrobial layer has a visually perceivable color that is differentfrom the color of the layer immediately below it.

With respect to the bioactive coated substrates 10 and 10′ of FIGS. 1and 2 , there are two scenarios by which the wear can be visuallydetected. In the first scenario, wearing away of both topcoat 16 andoutermost bioactive layer 16 is visually perceived because of thedifferent colors of top layer 16 and the layer immediately below the toplayer. In the second scenario, topcoat layer 18 and outermost bioactivelayer 16 can be of a sufficiently different color such that wearing awayof topcoat layer 18 is visually perceived.

In accessing color differences, it should be appreciated that theoutermost bioactive layer 14 and the layer immediately below theoutermost bioactive layer (as well as the substrate and other layers)can be characterized by Lab color space coordinates L*, a*, and b*relative to CIE standard illuminant D50. In a refinement, at least oneof Lab color space coordinates L*, a*, and b* relative to CIE standardilluminant D50 of the outermost bioactive layer differs from that of thelayer immediately below the outermost bioactive layer by at least inincreasing order of preference, 5%, 10%, 15%, 20%, 25% or 50%. Inanother refinement, each of the Lab color space coordinates L*, a*, andb* relative to CIE standard illuminant D50 of the outermost bioactivelayer differ from those of the layer immediately below the outermostbioactive layer by at least in increasing order of preference, 5%, 10%,15%, 20%, 25% or 50%. In a variation, Delta E (2000), which quantifiesthe distance between two points in the color space, can be used toquantify the difference between two colors. A visual or noticeabledistinction between two colors can be impacted by various factors,including the viewer, the texture, and gloss. In a refinement, a delta Egreater than or equal to 0.5 is a sufficient difference in color for theindicator. In another refinement, a delta E greater than or equal to 1.0is a sufficient difference in color. In still another refinement, adelta E greater than or equal to 2.0 is a sufficient difference.

Referring to FIGS. 3A and 3B, schematic cross-sections of a substratecoated with a bioactive material having macroparticles that extend intothe topcoat layer are provided. As set forth above, this coating systemof FIG. 2A can be used to form bioactive coated substrate 10 of FIG. 1A,while the precursor substrate 10 can be used to form bioactive coatedsubstrate 10 of FIG. 1B. With reference to FIG. 3A, precursor coatedsubstrate 30 includes a base substrate 12, outermost bioactive layer 16disposed over the substrate, a topcoat layer 18 disposed over thebioactive layer. FIG. 3A shows macroparticles 32 extends from outermostbioactive layer 16 and from first interlayer 14 into topcoat layer 18.Similarly, FIG. 3B shows that precursor coated substrate 30′ includes abase substrate 12, an optional base layer 22 disposed over thesubstrate, outermost bioactive layer 16 disposed over the substrate andbase layer if present, a topcoat layer 18 disposed over the outermostbioactive layer, and a plurality of alternating additional bioactivelayers 16′ and interlayers 14 interposed between base layer 22 andoutermost bioactive layer 16. Topcoat layer 18 is disposed overoutermost bioactive layer with the plurality of macroparticles extendinginto or embedded therein. FIG. 3B shows macroparticles 32 extending fromboth interlayers and from bioactive layers. In a refinement, theplurality of macroparticles have an average diameter d₂ of about 50 nmto 0.1 microns. The plurality of macroparticles 108 can be loosely boundto bioactive layers 16 and to topcoat layer 18 such that the pluralityof macroparticles 108 can be mechanically removed from the topcoat layer18. For example, the plurality of macroparticles 22 can be removed bywiping the surface of the topcoat layer 106 with a dry cloth. Therefore,removing the plurality of macroparticles 22 yields a plurality ofmicroscopic openings.

In another variation, an adhesion layer is disposed over the topcoatlayer with a hydrophobic coating is disposed over the adhesion layer.The adhesion layer can be composed of metal oxide such as silicondioxide (e.g., SiOx adhesion layer where ex is 0.5 to 1.2). In arefinement, the hydrophobic coating is composed of a polymeric materialselected from the group consisting of fluorinated monomers, fluorinatedoligomers, or fluorinated polymers. Typically, the hydrophobic coatingis a hydrophobic coating. In a refinement, the polymeric coatingincludes a self-assembling monolayer of the polymeric material. Aspecific example of such a hydrophobic coating is alkoxysilanefunctionalized perfluoropolyether. Advantageously, the alkoxysilanefunctionalized portion attaches to the adhesion layer with thehydrophobic tail portion aligning to each other. FIG. 4 depicts thisvariation in which adhesion layer 40 is disposed over and optionallycontacts coated substrate 10 or 10′ as set forth above. Hydrophobiccoating 42 is disposed over and optionally contacts adhesion layer 40.

In another embodiment, the bioactive coated substrate is included in anarticle. In a refinement, the useful article further includes anindicator layer as set forth above. Many healthcare or hospital surfacesmay greatly benefit from a bioactive coated substrate. For example,useful articles can include but are not limited to bedrails, footboards,bed-side tables, knobs, handles, safety rails, carts, push plates, kickplates, mop plates, stretcher plates, spigots, drains, sinks, faucets,drain levers, water fountain components, sanitizers/soap dispensers,hand dryers, commonly used buttons, headrest, showerheads, countertops,hinges, locks, latches, trim, toilet or urinal hardware, light switches,armrest, thermostat controls, telephones, floor tiles, ceiling tiles,wall tiles, instrument handles (e.g. drug delivery systems, monitoringsystems, hospital beds, office equipment, operating room equipment,stands and fixtures), IV poles, trays, pans, walkers, wheelchairs,keyboards, computer mouse surfaces, exercise equipment, rehabilitationequipment, physical therapy equipment, lamps, lighting systems, lids,hangers, remotes, cup holders, toothbrush holders, gown snaps, andwindow sills. Likewise, popular or common areas in general could benefitfrom articles with bioactive coated substrate s. For example, somearticles or surfaces can include but are not limited to shopping carts,shopping cart handles, child seats, handrails, register keypads,register housings, ATMs, lockers, elevator controls, paper toweldispensers, toilet paper dispensers, vending machines, and restroomsurfaces. Similar articles and surfaces can benefit in housing areas,mass transit, laboratories, religious gathering facilities, or anycommonly visited facilities. Other uses can include but are not limitedto writing utensils, eyeglass frames, combs, phone covers, tabletcovers, headphone, and bottle openers to name a few.

Referring to FIG. 4 , a flow chart depicting a method of forming thebioactive coated substrate set forth above is provided. The methodincludes step 60 of providing a base substrate. The method also includesstep 62 of applying a first interlayer over the base substrate. Thefirst interlayer has a plurality of macroparticles protruding from thesurface of the first interlayer. The first interlayer can be applied byPVD in a manner that results in the deposit of a plurality ofmacroparticles. Advantageously, the bioactive layer can be applied byCAE for this purpose. At step 64, the method includes a step of applyingan outermost bioactive layer over the first interlayer where theplurality of macroparticles extends into and typically through theoutermost bioactive layer. The outermost bioactive active layer can beapplied by PVD (e.g., sputtering, CAE). Finally, the method includes astep of applying a topcoat layer at step 66. In a refinement, thetopcoat layer can be applied by PVD. In a refinement, the topcoat layercan be applied by CAE. The method of applying a bioactive coatedsubstrate can further include step 68 in which the plurality ofmacroparticles is removed. Typically, the plurality of macroparticles ismechanically removed. For example, the plurality of macroparticles canbe removed by wiping with a dry cloth. In a refinement, the plurality ofmacroparticles can be removed by mass finishing the bioactive coatedsubstrate.

In a variation, a plurality of alternating additional bioactive layersand additional interlayers are deposited over the base substrate priorto deposition of the first interlayer. In a refinement, at least aportion of the macroparticles extends from one or more of the additionalinterlayers to the topcoat layer. In refinement, at least a portion ofthe macroparticles extends from one or more of the additional bioactivelayers to the topcoat layer. It should be appreciated that the layerthat grows particles therein can be deposited by PVD (i.e., CAE) in amanner that results in the deposit of a plurality of macroparticles.Advantageously, the bioactive layer can be applied by CAE. Properties,thickness, and compositions for the layers and microscopic openingsformed by the method of FIG. 4 are the same as those set forth above.

The following examples illustrate the various embodiments of the presentinvention. Those skilled in the art will recognize many variations thatare within the spirit of the present invention and scope of the claims.

A bioactive coated substrate including a stainless steel substratecoated with a copper oxide bioactive layer and a zirconium topcoat layerapplied by cathodic arc evaporation had superior antimicrobialperformance as compared with control substrates. The bioactive coatedsubstrate had superior performance as compared with a stainless steelcontrol substrate. As provided in Table 1, Cuprotesmo test was used todetermine the presence of copper ions (e.g. Cu(I) and Cu(II)). This isnot a direct test for bioactive or antimicrobial efficacy but withoutbeing bound by theory copper ions are believed to play a role is inhibitand/or destroy microbes. A reactive paper is used to determine thepresence of copper ions by changing colors. The color pink indicates thepresence of copper ions. Table 1 (FIG. 5 ) provides properties of thebioactive coated substrate (i.e., a bioactive coated onto a stainlesssteel substrate) along with a copper substrate (i.e., a penny) and astainless steel substrate.

The bioactive coated substrate was also tested for its antibacterialactivity and efficacy using the standard JIS 2801 method with a contactsurface time of 24 hours at 35° C. with E. Coli. The test was run inreference to the control and measured in colony-forming units (CFU) permilliliter (mL). As shown by Table 1, the bioactive coated substrate hasa lower quantity of colony-forming units by about 4.4 log countscompared with stainless steel, which indicates significant antimicrobialactivity.

Table 2 (FIG. 7 ) provides results for the growth of bacteria (i.e., S.aureus) on stainless steel, brass, a multilayer sample having a buriedactive layer with microscopic openings, and a sample with the bioactivelayer on top. The results show that the multilayer sample having aburied bioactive layer with microscopic openings provides excellentinhibition of bacterial growth that is comparable to brass and thesample with sample with the bioactive layer on top.

FIG. 8 provides top surface elemental mapping (EDS) showing that coppersublayers are exposed through the microscopic openings (i.e., pits).

FIG. 9 provides SEM cross-section images that copper sublayers and thefirst interlayer are exposed through the microscopic openings (i.e.,pits).

Example 1 (Multi-Layer with Copper Nitride)

A vacuum thin film deposition chamber is pumped down to a pressure of5.0e-5 Torr. The chamber is then heated to a temperature of 100 C usingwall mounted resistive heating elements. On a carousel inside thechamber, stainless steel door handles are mounted on racks that rotatein a 2-axis planetary motion in between a wall mounted magnetronsputtering cathode and a centrally located cylindrical arc cathode. Anion etch surface preparation is carried out by backfilling with Argongas to a pressure of 25.0 mTorr and a bias voltage of −500V is appliedto parts for 5 minutes. A first Zirconium metal adhesion layer isapplied to the handles by striking an arc on the arc cathode at acurrent of 300 A. The chamber is backfilled by Argon to a pressure of3.0 mTorr and a substrate bias of −50V is applied. This step lasts 5minutes to build a layer of 50 nm thick Zr metal. A second coating layercomprised of a Zirconium Nitride, is applied by continuing to run thearc on the Zr target but adding Nitrogen gas at flows of 150 sccm for acomposition of approximately ZrN_(0.50). This layer is built up toapproximately 10 nm in 1 minute. A third layer is applied by continuingto run the arc on the Zr target and flow the Argon and Nitrogen gaseswhile powering a Copper magnetron sputtering cathode to 9.5 kW. Thisstep lasts for 4 minutes to build a co-deposited mixed metal compoundlayer. In the third step, the Zirconium arc target is shut off while theCopper magnetron sputtering cathode remains on as does the flow of Argonand Nitrogen. This sputter-only step lasts for 30 minutes to build aCuN_(0.3) coating around 300 nm thick at which point the Cu sputteringcathode and the Nitrogen gas is shut off, leaving only Argon to continueto flow at a pressure of 3.0 mTorr. The shutter to the magnetronsputtering cathode is closed. After this, a fourth step of Zirconiummetal adhesion layer is applied to the handles by striking an arc on thearc cathode at a current of 300 A. The chamber is backfilled by Argon toa pressure of 3.0 mTorr and a substrate bias of −50V is applied for 5minutes to build a layer of 50 nm thick Zr metal. A fifth layer is addedcomprised of a Zirconium Nitride, which is applied by continuing to runthe arc on the Zr target but adding Nitrogen gas at flows of 150 sccmfor a composition of approximately ZrN_(0.50). This layer is built up toabout 300 nm in 20 minutes. A sixth and final layer is added comprisedof a Zirconium Oxide, which is applied by continuing to run the arc onthe Zr target but shutting off both the Argon and Nitrogen flow whileadding 500 sccm of Oxygen flow while maintaining a pressure of 1 mTorrto achieve a composition of approximately ZrO_(0.50) for 37 seconds todeposit approximately 10 nm.

Example 2 (Multi-Layer with Copper Oxide)

A vacuum thin film deposition chamber is pumped down to a pressure of5.0e-5 Torr. On a carousel inside the chamber, chrome plated brassfaucet spouts are fixtured on a rack that rotates on a single axisbetween the chamber wall mounted arc cathode and a centrally locatedcylindrical arc cathode. An ion etch surface preparation is carried outby backfilling with Argon gas to a pressure of 25.0 mTorr and a biasvoltage of −500V is applied to parts for 5 minutes. A Copper Oxide layeris applied to the spouts by striking an arc on a Copper arc wall mountedcathode at a current of 350 A. The chamber is backfilled by Oxygen to apressure of 2.0 mTorr and a substrate bias of −50V is applied. This steplasts 8 minutes to build a layer of 200 nm thick Copper Oxide for anapproximate composition of CuO_(0.3). A second coating layer is appliedto the spouts by striking an arc on a Zirconium arc cathode at a currentof 460 A. The chamber is backfilled by Argon to a pressure of 3.0 mTorrand a substrate bias of −50V is applied. This step lasts 3 minutes tobuild a layer of 50 nm thick of zirconium as an adhesion layer. A finallayer is added comprised of a zirconium oxycarbide, which is applied bycontinuing to run the arc on the Zr target but shutting off the Nitrogenflow while adding 200 sccm of Oxygen and 100 sccm of methane flow whilemaintaining a pressure of 3 mTorr to achieve a composition ofapproximately ZrO_(0.35)C_(0.15). This final layer is built up to 300 nmin 20 minutes.

Example 3 (Zr and CuO_(x) Multilayer Coating)

A vacuum thin film deposition chamber is pumped down to a pressure of8.0e-5 Torr. Inside the chamber, stainless steel panels are mounted onracks that rotate in a 2-axis planetary motion between a wall mountedCopper magnetron sputtering cathode and a centrally located cylindricalarc Zirconium cathode. An ion etch surface preparation is carried out bybackfilling with Argon gas to a pressure of 30.0 mTorr and a biasvoltage of −500V is applied to parts. This step lasts 2.5 minutes afterwhich the Argon gas is lowered to a pressure of 3.0 mTorr and asubstrate bias of −50V is applied. A Zirconium adhesion layer is appliedto the panels by striking an arc on the arc cathode at a current of 300A. This step lasts 10 minutes to build a layer of 250 nm thickZirconium. Then, the arc is turned off and oxygen gas is added to a flowrate of 60 sccm while maintaining the pressure of 3.0 mT. Then, theCopper magnetron sputter cathode is turned on to a power of 5 kW for 20minutes to build a layer of copper oxide to a thickness of 2000 nm.Then, the Copper sputtering target is turned off, along with the oxygengas, and the zirconium arc target is turned back on for 10 min at acurrent of 300 A for the final zirconium coating. The resulting film isa total of 2500 nm thick.

While exemplary embodiments are described above, it is not intended thatthese embodiments describe all possible forms of the invention. Rather,the words used in the specification are words of description rather thanlimitation, and it is understood that various changes may be madewithout departing from the spirit and scope of the invention.Additionally, the features of various implementing embodiments may becombined to form further embodiments of the invention.

What is claimed is:
 1. A bioactive coated substrate comprising: a basesubstrate; a first interlayer disposed over the base substrate; anoutermost bioactive layer disposed on the first interlayer; and atopcoat layer disposed on the outermost bioactive layer, wherein aplurality of microscopic openings extending through the topcoat layerand the outermost bioactive layer to expose the first interlayer and theoutermost bioactive layer, the plurality of microscopic openingsoriginating in the first interlayer.
 2. The bioactive coated substrateof claim 1, wherein the plurality of microscopic openings have anaverage width of about 100 nm to 10 microns.
 3. The bioactive coatedsubstrate of claim 1, wherein the plurality of microscopic openingsincludes an opening type selected from the group consisting of pores,pinholes, pits, and combinations thereof.
 4. The bioactive coatedsubstrate of claim 1, wherein the outermost bioactive layer has athickness from about 50 to 1500 nm and the topcoat layer has a thicknessfrom about 50 to 1500 nm.
 5. The bioactive coated substrate of claim 1,wherein the outermost bioactive layer is composed of a componentselected from the group consisting of copper metal, copper alloy, copperoxides, copper nitrides, copper oxides containing carbon atoms, andcombinations thereof.
 6. The bioactive coated substrate of claim 1,wherein the outermost bioactive layer is composed of CuO_(x), where x isfrom 0.1 to 1.0.
 7. The bioactive coated substrate of claim 1, whereinthe outermost bioactive layer is composed of CuO_(a)N_(b), where a isfrom 0.0 to 1.2 and b, is from 0.01 to 0.4.
 8. The bioactive coatedsubstrate of claim 1, wherein the outermost bioactive layer is composedof CuO_(c)C_(d), where c is from 0.0 to 1.2 and d, is from 0.01 to 0.4.9. The bioactive coated substrate of claim 1 further comprising a baselayer interposed between the base substrate and the outermost bioactivelayer.
 10. The bioactive coated substrate of claim 9, wherein the baselayer has a thickness from about 20 to 300 nm.
 11. The bioactive coatedsubstrate of claim 10 further comprising a multilayer stack thatincludes one or more additional bioactive layers alternating with one ormore additional interlayers, the multilayer stack being interposedbetween the base substrate and to the first interlayer, whereinadditional microscopic openings extends to an opening bottom in the oneor more additional interlayers such that each bioactive layer above theopening bottom and each interlayer above the opening bottom is exposed.12. The bioactive coated substrate of claim 11 comprising 1 to 10additional bioactive layers and 1 to 10 additional interlayers
 22. 13.The bioactive coated substrate of claim 12, wherein the base layer, thefirst interlayer, and the additional interlayers are independentlycomposed of a compound having formula:M_(1-x-y)C_(x)N_(y) where M is zirconium or titanium and x is 0.0 to 0.3and Y is 0.1 to 0.5.
 14. The bioactive coated substrate of claim 10,wherein the base layer, the first interlayer, and the additionalinterlayers are independently of a compound having formula:M_(1-x-y)O_(x)C_(y). where M is zirconium or titanium and x is 0.1 to0.4 and y is 0.5 to 0.2.
 15. The bioactive coated substrate of claim 10,wherein the additional bioactive layers are composed of copper metal,copper alloys, or copper-containing compounds, the copper-containingcompounds including copper atoms in a +1 or +2 oxidation state orcombinations of copper atoms thereof.
 16. The bioactive coated substrateof claim 10, wherein the topcoat layer is composed of a componentselected from the group consisting of carbides, gold, graphite,nitrides, platinum, titanium, titanium nitride, Zr, ZrN, ZrCN, ZrON,ZrO₂, ZrOC, Cr, CrN, CrCN, Ti, TiN, TiCN, TiON, TiO₂, and TiOC, andcombinations thereof.
 17. The bioactive coated substrate of claim 10,further comprising a hydrophobic coating disposed over the topcoatlayer, wherein the hydrophobic coating is composed of a polymericmaterial selected from the group consisting of fluorinated monomers,fluorinated oligomers, or a fluorinated polymers.
 18. The bioactivecoated substrate of claim 17, wherein the hydrophobic coating includes aself-assembling monolayer of the polymeric material.
 19. A method ofproducing a bioactive coated substrate comprising: providing a basesubstrate; depositing a first interlayer over the base substrate, thefirst interlayer having a plurality of macroparticles protruding from asurface of the first interlayer; depositing an outermost bioactive layerover the first interlayer, the plurality of macroparticles extendinginto the outermost bioactive layer; depositing a topcoat layer on theoutermost bioactive layer, the plurality of macroparticles extendinginto the topcoat layer; and removing at least a portion of the pluralityof macroparticles to form a plurality of microscopic openings in thetopcoat layer.
 20. The method of claim 19, wherein the outermostbioactive layer is composed of a component selected from the groupconsisting of copper metal, copper oxides, copper nitrides, copperoxides containing carbon atoms, and combinations thereof.
 21. The methodof claim 20, wherein the outermost bioactive layer is applied bycathodic arc evaporation.
 22. The method of claim 20, wherein the firstinterlayer is applied by cathodic arc evaporation.
 23. The method ofclaim 19 wherein a plurality of alternating additional bioactive layersand additional interlayers are deposited over the base substrate priorto deposition of the first interlayer.
 24. The method of claim 23wherein at least a portion of the macroparticles extend from one or moreof the additional interlayers to the topcoat layer.
 25. The method ofclaim 23 wherein at least a portion of the macroparticles extend fromone or more of the additional bioactive layers to the topcoat layer.